tbuckley/cabot-search huggingface dataset:
Abstract 9592: The Super Relaxed State of Myosin Contributes to the Pathogenesis of Right Ventricular Dysfunction in Pulmonary Hypertension
Authors: Mark T Waddingham, Hirotsugu Tsuchimochi, Ryotaro Asano, Takashi Sonobe, Takahiro Higuchi, Kohki Aoyama, Mikiyasu Shirai, James T Pearson, Takeshi Ogo
Journal: Circulation (2022)

Introduction: Patients with pulmonary hypertension (PH) often succumb to right ventricular (RV) failure yet little is known regarding the underlying pathological mechanisms. Recently, the transition of myosin from the disordered relaxed (DRX) to the super relaxed (SRX) state during diastole has been identified as a pathological feature contributing to myocardial dysfunction in heart failure. Using synchrotron radiation (SR) x-ray diffraction (SAXS), the proximity of myosin heads relative to actin in the in situ beating rat heart can be evaluated in different layers of the myocardial wall. We performed SR SAXS at different timepoints post-PH induction with simultaneous PV-loop acquisition to assess if SRX transition contributes to progressive global RV dysfunction in a rat model of PH. Methods: PH was induced in rats using the Sugen5416/3-week 10% hypoxia method, with rats being returned to normoxia for 3- (SuHx3wk) or 6-weeks (SuHx6wk) after the hypoxic period. SR SAXS was performed at BL40XU, SPring-8 Synchrotron, Japan. Global and site-specific RV myofilament phosphorylation status was also examined. Results: Compared to control rats (n=7), SuHx3wk (n=7) and SuHx6wk (n=7) rats exhibited progressive increases in RV size, RV end systolic pressure (ESP), RV dP/dt max and dP/dt min (all P&lt;0.05 vs. Control). In the deeper subendocardial layer of the RV free wall, there were virtually no myosin heads within the proximity of actin at end diastole in SuHx6wk rats, whereas in the control and SuHx3wk rats, around 30-50% of myosin heads were in proximity to actin (P&lt;0.05, SuHx6wk vs. Control and SuHx3wk). No significant differences in diastolic sarcomere length were found, suggesting a transition of myosin from DRX to SRX in the SuHx6wk rats. Importantly, indices for global RV function (ESP, dP/dt max, dP/dt min ) significantly correlated with diastolic myosin mass transfer values. Analysis of RV myofilament phosphorylation revealed a progressive and significant reduction in MLC-2v phosphorylation over the time course of PH in rats. Conclusion: PH is associated with progressive changes in global RV function, which may be attributed to a transition from DRX to SRX state of myosin in the RV. Reduced MLC-2v phosphorylation may underlie the DRX to SRX transition in PH.
Abstract 9920: Utilizing Synchronous Healthcare Delivery to Optimize the Use of Guideline Directed Medical Therapies in Patients With Type 2 Diabetes: Results From the DECIDE-CV Clinic
Authors: Tara Gedeon, Amale Ghandour, Guang Zhang, Amir Razaguizad, Sharmila Balram, Tricia Peters, Rita Suri, Ivan G Fantus, Nadia Giannetti, Atul Verma, Thomas Mavrakanas, Michael Tsoukas, Abhinav Sharma
Journal: Circulation (2022)

Introduction: The high burden of comorbidities among patients with Type 2 Diabetes (T2D) may contribute to the low use of guideline directed medical therapies (GDMT) that improve CV outcomes, including sodium glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like-peptide-1 receptor agonists (GLP1RA). Hypothesis: The DECIDE-CV clinic at McGill University (Montreal, Canada) is a novel synchronous healthcare program whereby patients with T2D are seen at each visit simultaneously by a cardiologist, endocrinologist, and nephrologist to enable rapid GDMT implementation. We hypothesized that synchronous healthcare delivery would increase SGLT2i and GLP1RA use among multimorbid patients with T2D. Methods: We conducted a pre/post analysis of GDMT use throughout patient follow-up in the DECIDE-CV clinic. We evaluated the first 76 patients (2020-10-26 to 2022-04-18) and used Canadian diabetes/CV guidelines with Quebec medication coverage criteria to assess eligibility for SGLT2i and GLP1RA. A 2-sample test for proportions compared use of GDMT at baseline and follow-up. Results: At baseline, the mean age of patients was 68.5 years old, 79% were male, 33% were non-white minorities, 50% had CKD, 64% had HF, and 58% had ASCVD. The median eGFR was 60.1 ml/min/1.73m 2 (IQR 40.7, 93.8), median NT-proBNP was 434 (IQR 123, 1425), and median HbA1c was 7.3% (IQR 6.8, 8.7). At baseline only 37% were prescribed a SGLT2i and 3% a GLP1RA despite being guideline eligible and having medication coverage. After the first visit, the use of therapies significantly increased to 90% for SGLT2i and 39% for GLP1RA. At the end of follow-up, 98% were prescribed a SGLT2i and 57% were prescribed a GLP1RA (P-value comparing proportion GDMT &lt; 0.001; Figure 1). Conclusions: Among patients eligible for GDMT, the initial use of SGLT2i and GLP1RA was low. Our model of synchronous healthcare delivery in a multi-comorbid population, significantly increased the use of SGLT2i and GLP1RA.
Abstract 9753: Outcomes of Substance Abuse Among Patients With Takotsubo Cardiomyopathy
Authors: Ayesha Shaik, Karthik Gonuguntla, Shivaraj Patil, yasar sattar, Chaitanya Rojulpote, Muhammad Zia khan, Sudarshan Balla
Journal: Circulation (2022)

Introduction: Takotsubo cardiomyopathy (TC) is a reversible cardiomyopathy that is precipitated by emotional or physical stress mediated by catecholamines. Drugs that modulate adrenergic tone can precipitate/ worsen TC Hypothesis: To compare the prevalence of comorbidities and incidence of complications in TC patients with substance abuse (SA) compared to those without SA Methods: The United States NIS data from 2016 to 2018 was queried to identify adult patients (≥18 years) with TC using ICD 10 code. SA was defined as use of opiates or cannabis or cocaine. Chi- square test was applied for statistical analysis Results: We identified a total of 23, 220 patients with TC. 5.3% had history of SA. The prevalence of opioid, cannabis and cocaine use was 2.4 %, 2% and 1% respectively. Comparing the two groups (SA vs no SA), mean age was 56.8y vs 67.3y. the prevalence of hypertension (56% vs 67%; p&lt;0.001), diabetes (15% vs 19%; p=0.007), and obesity (11 % vs 13%; p=0.04) atrial fibrillation (7 % vs 13.6%; p&lt;0.001) coronary artery disease (50% vs 54%; p= 0.02) were lower. The prevalence of any psychiatric disorder (60.6% vs 38.2%; p&lt;0.001), heart failure (36% vs 31%; p &lt;0.001), chronic obstructive pulmonary disease (36% vs 28.5%; p &lt;0.001), tobacco use (71% vs 42%; p&lt;0.001) and alcohol use(11.4% vs 4%; p &lt;0.001) were higher. Outcomes were (SA vs no SA)- cardiogenic shock (2.4% vs 3%; p =0.31), mechanical ventilation (9% vs 4.5%; p&lt; 0.001), acute kidney injury (3% vs 8.4%; p &lt;0.001), cardiac arrest (2.8% vs 1.5%; p &lt;0.001), mitral regurgitation (4.5% vs 6.4%; p =0.007), ventricular tachycardia (5.7% vs 3.3%;p&lt; 0.001) ventricular fibrillation (2% vs 1%;p &lt;0.001) Conclusions: TC patients with SA had a lower cardiovascular risk factors such as hypertension, type 2 diabetes, obesity, high burden of psychiatric disorders, high rates of in hospital complications like need for mechanical ventilation, cardiac arrest and ventricular arrhythmias but no difference in the rates of cardiogenic shock compared to no SA group. Prospective studies are needed to confirm the impact of SA disorder on incidence and outcomes of TC in this cohort
Abstract 9837: Outcomes of Thirty Day Readmission in Patients With Heart Failure on Index Hospitalization Undergoing Transcatheter Aortic Valve Replacement (TAVR): Insights From the United States Nationwide Readmission Database
Authors: Salman Zahid, Anas Hashem, Varunsiri Atti, Hameed Ullah, Fnu Salman, Mansoor Rahman, Mohammad Kawsara, Muhammad Z Khan, sudarshan balla
Journal: Circulation (2022)

Introduction: Heart failure (HF) remains one of the most common cardiac comorbidity among patients undergoing Transcatheter Aortic Valve Implantation (TAVR). Hypothesis: Patients with acute HF at index admission hospitalized for TAVR have worse 30-day readmission outcomes. Methods: We used the United States Nationwide Readmission Database to identify patients undergoing TAVR from 2015 to 2019 using ICD 10 codes. Results: A total of 246,211 weighted hospitalizations for TAVR were included in the analysis, out of which 83,347 (33.9%) had heart failure on index hospitalization. The median age of patients without AHF was 81 years [IQR: 75-86] and 82 years for those with AHF [IQR: 75-87], p=0.02. The burden of comorbidities in terms of chronic kidney disease, end-stage renal disease, and heart failure with reduced and preserved ejection fraction was higher for patients with AHF on index admission. Among patients who got readmitted at 30-days, readmission rate (12.3% vs. 10.4%, p&lt;0.01) and 30-day readmission mortality (5.4% vs. 3.0% , p&lt;0.01) were higher in patients with AHF on index admission. Similarly, patients with AHF had higher rates of acute kidney injury, cardiogenic shock, need for an Intra-aortic balloon pump, and Impella at 30-day readmissions. In terms of resource utilization, length of stay (LOS) increased by one day and the cost of re-hospitalization was higher with AHF ($9,227 vs. $8,910, p=0.01). Kaplan Meier survival curve showed reduced survival at 30-days for patients who had AHF on index admission (log-rank test p&lt;0.01) Conclusions: We report worse 30-day readmission outcomes in terms of higher mortality, readmissions, and resource utilization in TAVR index hospitalizations complicated by AHF. Further studies are needed to better understand the risk predictors and interventions to prevent adverse outcomes in this higher-risk cohort undergoing TAVR.
Abstract 9838: Safety and Feasibility of Staged or Concomitant Transcatheter Edge-to-Edge Mitral Valve Repair After Transcatheter Aortic Valve Replacement
Authors: Salman Zahid, Anas Hashem, Muhammad Z Khan, sudarshan balla
Journal: Circulation (2022)

Introduction: The data on safety and feasibility of performing concomitant or staged Transcatheter Edge-to-Edge Repair (TEER) of the mitral valve with Transcatheter Aortic Valve Replacement (TAVR) remains limited. Hypothesis: Methods: The Nationwide Readmission Database (NRD) was utilized to identify TEER and TAVR procedures from 2015, to 2019, using ICD-10-CM administrative claim codes. Results: A total of 28,180 weighted cases of TEER were included in the analysis. Of the included cases 27,562 underwent TEER as a separate procedure and were compared with TEER cases performed concomitantly with TAVR (n=174) or performed as a staged procedure (n=453). In terms of crude outcomes, in-hospital mortality (4.4% vs 2.1%, p&lt;0.01) and associated complications including cardiogenic shock (8.5% vs 4.5%, p&lt;0.01), acute kidney injury (27.7% vs 15.2%, p&lt;0.01) and pacemaker implantation rates (3.7% vs 0.6%, p&lt;0.01) were higher for concomitant or staged procedures. However, in the propensity matched group there was no difference between the two groups in terms of in-hospital mortality (4.4% vs 6.2%, p0.13) and associated complications. Furthermore, in the matched group there was no difference in terms of hospital length of stay (3 days vs 3 days, p0.21) and hospitalization cost (USD 49,356 vs USD 49,037, p0.46) for TEER alone compared with concomitant or staged TEER procedures. Conclusions: TEER performed in the same admission as TAVR or as a staged procedure maybe safe and a feasible treatment option for patients with concomitant mitral regurgitation and severe aortic stenosis compared with TEER alone.
Abstract 9834: Lysosomal Ca <sup>2+</sup> Release Contribute to Arrhythmia After Myocardial Infarction
Authors: An Xie, Gyeoung-Jin Kang, Hong Liu, Eun Ji Kim, Feng Feng, Samuel C Dudley
Journal: Circulation (2022)

Introduction: In heart failure (HF), mitochondria Ca 2+ handling is involved in arrhythmogenesis by modulating diastolic sarcoplasmic reticulum (SR) Ca 2+ release. Recently, it has been reported that lysosomal Ca 2+ release can trigger a SR Ca 2+ release. Hypothesis: We investigated whether lysosomal Ca 2+ flux could contribute to ischemic HF arrhythmia in a similar manner to mitochondria. Methods: Ischemic HF was induced in wild type FVB/NJ mice by ligated left anterior descending coronary artery. Mice were studied at three weeks after myocardial infarction (MI). Results: The lysosomal-restricted transient receptor potential mucolipin 1 (TRPML1) Ca 2+ release channel, but not the two-pore channel 2, was significantly upregulated by 84.8% in cardiac border zone and 55.4% in a remote zone after MI, and cardiomyocyte TRPML1 was significantly increased in human patients with ischemic or nonischemic cardiomyopathy. As expected, TRPML1 co-localized with the lysosome marker, LAMP1. The master transcriptional lysosomal regulator, dephosphorylated TFEB (i.e., active TFEB) and LAMP1 labelled lysosomes increased after MI. Lysosomal Ca 2+ release directly as indicated by GCaMP7-TRPML1, a fluorescent Ca 2+ sensor coupled to TRPML1, was upregulated in MI mouse CMs. TRPML1 specific agonist, ML-SA1, could evoke Ca 2+ sparks in the CMs isolated from MI mice, and these sparks were inhibited by a specific antagonist, ML-SI1. Furthermore, thapsigargin or high concentration ryanodine, inhibited Ca 2+ loading and release from the SR respectively and prevented TRPML1-dependent Ca 2+ sparks in the MI CMs. TRPML1-dependent sparks were not affected by S107, a drug which specifically inhibits Ca 2+ leak, however. Blocking TRPML1depressed early and delayed afterdepolarizations (EADs and DADs) in CMs isolated from MI mice while increasing TRPML1 activity enhanced triggered activity. The inhibition of TRPML1 had no effect on the APs recorded from sham mouse CMs, however. ML-SA1 could increase induced ventricular fibrillation episodes in MI mice while ML-SI1 could reduce arrhythmia by optical mapping and pacing. Conclusions: Lysosomes contribute to arrhythmic risk in MI by releasing Ca 2+ during diastole causing SR diastolic Ca 2+ release and triggered activity.
Abstract 9902: Relationship Between Preoperative Hemodynamics, Fenestration, and Fontan Hospitalization Length of Stay
Authors: Garick D Hill, Matthew Ferguson, Saul Flores, Salil Ginde, Kevin D Hill, Michael Johansen, Jane W Newburger, Zhiqian Gao, James F Cnota
Journal: Circulation (2022)

Introduction: Using a multi-center Pediatric Heart Network dataset linking surgical (STS) and catheterization (IMPACT) data, we sought to evaluate factors associated with use of Fontan fenestration and the impact of fenestration on post-Fontan length of stay (LOS) in the context of pre-operative hemodynamics. Methods: Centers participated using a data sharing agreement permitting linkage of de-identified STS and IMPACT data. Patients 2-6 years old at Fontan surgery from 2010-2020 with catheterization &lt;1 year prior were included. Multivariable logistic regression was used to evaluate factors associated with fenestration. Full model covariates included center, ventricular morphology, Fontan type (lateral tunnel [LT] vs extracardiac conduit [ECC]), age at Fontan, sex, race and hemodynamic variables. Post-Fontan LOS was analyzed by fenestration status across hemodynamic variables using non-parametric ANOVA and by multivariable linear regression. Results: The cohort included 702 patients (7 centers). Median age at Fontan was 3.4 years (IQR 2.7-4.2) with fenestration used in 465 (66.2%). In multivariable modeling, factors associated with fenestration included center (range 27-93% use, p&lt;0.0001), Fontan type (OR 14.1 for LT, p&lt;0.0001) and ventricular morphology (P=0.007). Addition of hemodynamic variables (mean pulmonary artery pressure [mPAP], end diastolic pressure and pulmonary vascular resistance index) did not improve the model (Figure). While Fenestration was independently associated with a decreased LOS (p=0.04), exploratory analysis demonstrated the benefit was most pronounced at mPAP ≥ 13mmHg (median 9 vs 12 days, p=0.001). Conclusions: There is wide center variability in use of Fontan fenestration that is not explained by pre-operative hemodynamics. Fenestration is independently associated with shorter LOS but those with mPAP ≥ 13 mmHg at pre-Fontan catheterization benefit the most from fenestration with shorter post-Fontan LOS.
Abstract 9841: Outcomes Following Biventricular Repair of Atrioventricular Septal Defect With a Single Left Ventricular Papillary Muscle
Authors: Scarlet Woodrick, Kellianne Kleeman, Sunkyung Yu, Ray Lowery, Jennifer Romano, Carlen G Fifer
Journal: Circulation (2022)

Introduction: In patients with atrioventricular septal defect (AVSD) with single papillary muscle attachments in the left ventricle (LV), the left AV valve (LAVV) is at risk for suboptimal repair. This study aimed to evaluate outcomes following repair of AVSD with single LV papillary muscle attachments and to identify preoperative predictors of postoperative LAVV outcomes. Methods: All patients with AVSD and anatomically or functionally single LV papillary muscle who underwent biventricular repair at our institution from 07/01/2000 - 07/01/2020 were retrospectively reviewed. Univariate analysis was used to identify associations between patient demographics, preoperative echocardiographic measures, and surgical characteristics with the degree of LAVV stenosis or regurgitation postoperatively and the need for reintervention on the LAVV. Results: Of 38 patients included, nearly all (97%) were repaired with no or partial closure of the LAVV cleft. Freedom from LAVV reintervention was 91% and 84% at 1 and 3 years. Five patients (13%) required reintervention on the LAVV with a median time to reintervention of 3.3 months post-AVSD repair; indication was LAVV regurgitation for four of the five patients. Preoperative LAVV regurgitation &gt; mild was associated with an increased risk for LAVV reintervention (p= 0.02). At discharge, 63% of patients had &gt; mild LAVV regurgitation and 5% had &gt; mild LAVV stenosis. At most recent follow-up, 32% had &gt; mild LAVV regurgitation and 12% had &gt; mild LAVV stenosis. Patients with younger age at repair and preoperative AV valve index &lt;0.67 had significantly increased risk of &gt; mild LAVV regurgitation at discharge (p=0.01 and p=0.04, respectively), however this did not persist at most recent follow-up. More pronounced unbalance of the AVSD was not associated with postoperative LAVV stenosis. Conclusions: Despite concern for repair in patients with AVSD and single papillary muscle attachments, surgical outcomes are favorable with low risk for reintervention. Risk of LAVV stenosis is low when repair of LAVV cleft is modified. Preoperative LAVV regurgitation, younger age at repair, and more pronounced unbalance of the AVSD predicted early postoperative LAVV regurgitation, with improvement over time.
Abstract 9861: Geographic Variation in Prescription of Heart Failure Guideline Directed Medical Therapies for United States Veterans is Prevalent Nationwide
Authors: Revanth Kosaraju, Gregg C Fonarow, Michael K Ong, Paul A Heidenreich, Donna L Washington, Xiaoyan Wang, Boback Ziaeian
Journal: Circulation (2022)

Introduction: In patients with heart failure with reduced ejection fraction (HFrEF), use of guideline directed medical therapies (GDMT) reduces mortality. Whether there is geographic variation in GDMT prescribing is not well-characterized. Hypothesis: We assessed the hypothesis that there is wide geographic variation nationally within the Veterans Affairs (VA) healthcare system for the receipt of GDMT. Methods: We linked the primary residence address of a cohort of Veterans with HFrEF receiving care at VA facilities (n=178,856) to hospital referral regions (HRRs). Using VA and non-VA pharmacy data between July 1, 2020 and July 1, 2021, we defined receipt of GDMT. For each HRR, we calculated the percentage of eligible Veterans that were prescribed each class of GDMT and a composite GDMT z-score. Lastly, we constructed national choropleth maps to depict HRR geographic variation in composite z-scores and prescription of each class of GDMT. Results: There was significant variation in individual GDMT class prescription and composite score across HRRs as shown in choropleth maps ( Figure) . Within HRRs, beta-blocker prescription was highest, with a median 80% of Veterans (interquartile range [IQR] 77.3% to 82.2%), afterload-reducing agents including angiotensin converting enzyme inhibitor / angiotensin receptor blocker / angiotensin receptor-neprilysin inhibitors (ARNI) 69.3% (IQR 66.4% to 72.1%), mineralocorticoid receptor antagonists (MRA) 29.2% (IQR 25.8% to 33.9%), sodium-glucose cotransporter 2 inhibitors (SGLT2I) 10.3% (IQR 7.7% to 12.8%), and ARNI 12.2% (IQR 8.6% to 15.3%). HRRs with the highest and lowest composite scores were often found in the same U.S. Census Regions. Conclusions: In conclusion, wide geographic disparities are present for GDMT prescribing to Veterans across HRRs. Veteran receipt of ARNI, SGLT2I, and MRA is low nationwide. Targeted approaches may be necessary to improve GDMT prescription for Veterans in lower performing HRRs.
Abstract 9856: Gender and Racial Disparities in Reported Cardiac Arrest Death in United States, 1999 to 2019
Authors: Carlos F Matute Martinez, Muhammad Qudrat Ullah, Muhammad Usman, Muhammad Usman Almani, Karla Inestroza, Juan G Sierra, Ahmad Hamdan, Mandeep Sidhu, Prince Ernest, Alejandro J Herrera-Ramos, Pablo Amador, Felipe Jose J Matute Martinez, Laura Rojo Grajales, Mark Davis
Journal: Circulation (2022)

Introduction: Cardiac arrest (CA) is the cessation of cardiac mechanical activity confirmed by the absence of signs of circulation. Data suggest that race and gender could impact the survival rate of CA (1,2). We aim to describe the temporal trend of the age-adjusted mortality rate of gender and race reported as any-mention cause of cardiac arrest death from 1990 to 2019. Methods: The United States statistics mortality data from the CDC WONDER database from 1999 to 2019 were used. The diagnosis of CA was stablished using the ICD-10 codes: I46.0, I46.1, I46.9 and I49.0. Mortality rate was calculated for all ages. Age-adjusted mortality rates per 100000 were calculated using 95% confidence intervals. Results: The study included 7435677 subjects with any-mention of CA death. Most deaths occurred in older individuals (90.7 % of the death reported in those 55 years or older). Cardiac Arrest deaths decreased from 138.1 in 1999 to 91.5 in 2019. Temporal trend depicted a gradual decline in the age-adjusted mortality rate per year (IRR 0.97 95 % CI 0.95 to 0.99). There was a progressive decrease mortality rate across both male (167.6 in 1999 to 110 in 2019 IRR 0.97 95% CI 0.96 to 0.98) and female (117.5 1999 to 76.5 in 2019 IRR 0.97 95% CI 0.96 to 0.98). The age-adjusted mortality rate was significantly higher in males compared to females (126.7 vs 91.3 IRR 1.39 95 % CI 1.27 to 1.52). There was a significant decrease in the mortality rate through 1999 to 2019 seen in all the races. Conclusions: There was an association in the CA mortality rate that persisted over the years favoring male over females. The Black race had the highest mortality rate among the races. American Native had the lowest mortality rate. The phenomenon underlying the race difference is not fully understood (3). Quality-improvement efforts have been associated with improvement of survival (4,5). The present data demonstrates a gradual decline of CA-related mortality associated with significant high gender and racial disparities.